1. Field of the Invention
The invention relates to predictive models for determining the extent of coronary artery disease (CAD) risk based on marker expression measurements, to their methods of use, and to computer systems and software for their implementation.
2. Description of the Related Art
Mortality and morbidity from CAD and myocardial infarction (MI) are a major global health burden. Major determinants of current CAD likelihood are sex, age, and chest-pain type.1, 2 Other risk factors such as diabetes, smoking, dyslipidemia, and family history have been associated with future cardiovascular event risk.3 In addition, atherosclerosis has a systemic inflammatory component including activation and migration of immune cells into the vessel wall.1, 5 In fact, since such cells are derived from and have interactions with circulating blood, quantitative measurements of circulating blood cell gene expression reflects the extent of CAD.6, 7 These observations likely reflect both changes in cell type distributions, which have prognostic value for cardiovascular events8 and gene expression changes within a specific cell type or lineage.
The “gold standard” for detecting CAD is invasive coronary angiography; however, this is costly, and can pose risk to the patient. Prior to angiography, non-invasive diagnostic modalities such as myocardial perfusion imaging (MPI) and CT-angiography may be used, however these have complications including radiation exposure, contrast agent sensitivity, and only add moderately to obstructive CAD identification.9, 10 
Unmet Clinical and Scientific Need
A non-invasive blood test that could reliably identify patients with CAD would have significant clinical utility. As such, a major advancement in the fight against atherosclerosis would be the development of non-invasive diagnostic tests that can aid in the diagnosis and assessment of the extent of CAD in patients. Herein the development and validation of an algorithm using marker expression and clinical factors (e.g., age and gender) for such a purpose is described.